1. Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a phase I clinical trial.
- Author
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Bellon G, Michel-Calemard L, Thouvenot D, Jagneaux V, Poitevin F, Malcus C, Accart N, Layani MP, Aymard M, Bernon H, Bienvenu J, Courtney M, Döring G, Gilly B, Gilly R, Lamy D, Levrey H, Morel Y, Paulin C, Perraud F, Rodillon L, Sené C, So S, Touraine-Moulin F, and Pavirani A
- Subjects
- Adolescent, Adult, Blotting, Southern, Bronchoalveolar Lavage, Cystic Fibrosis Transmembrane Conductance Regulator analysis, Cystic Fibrosis Transmembrane Conductance Regulator genetics, DNA analysis, Female, Gene Expression genetics, Genetic Vectors genetics, Humans, Immunohistochemistry, Male, Nasal Mucosa cytology, Nasal Mucosa metabolism, Polymerase Chain Reaction, RNA, Messenger analysis, Adenoviridae metabolism, Aerosols therapeutic use, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Genetic Therapy
- Abstract
Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator (CFTR), was administered by aerosolization in a single escalating dose to three pairs (cohorts) of cystic fibrosis (CF) patients. Buffer only was administered to the nose and lungs 9-14 days before nasal instillation of virus followed the day after by aerosolization of Ad CFTR to the lung. Nasal doses (defined in terms of viral plaque forming units, pfu) were 10(5), 10(7), and 4 x 10(8), whereas aerosolized doses were 10(7), 10(8), 5.4 x 10(8) for each cohort, respectively. No acute toxic effects were observed in the first 4 weeks after virus treatment. Shedding of infectious Ad CFTR was never detected, whereas detection of vector DNA sequences and CFTR expression demonstrated DNA transfer to the nose and airways of patients. No significant deviations in immunological and inflammatory parameters were observed in serum and in bronchoalveolar lavage (BAL). Importantly, for all patients, the serum anti-adenovirus antibody levels did not change significantly from baseline and no antibodies against adenovirus were found in BAL.
- Published
- 1997
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